COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)
Study Details
Study Description
Brief Summary
This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) >/ = 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and >/= 65 years of age) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (>/= 65 years of age) and approximately 20% to have had confirmed COVID-19.The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) >/= 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and >/= 65 years of age) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (>/= 65 years of age) and approximately 20% to have had confirmed COVID-19. This is an adaptive design and may add arms of new vaccine platforms and/or variant lineage spike vaccines as needed. The study arms will be conducted in different stages (that could overlap) depending on public health needs and the availability of study products (starting with the available mRNA vaccines). The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination. The secondary objective is to evaluate the safety of candidate SARS-CoV-2 variant vaccines, as assessed by: a) Local and systemic solicited Adverse Events for 7 days following each vaccine dose; b) Unsolicited Adverse Events from Dose 1 to 28 days following each vaccine dose; c) Serious Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interests (AESIs), New Onset of Chronic Medical (NOCMCs) and Adverse Events (AEs) leading to withdrawal from the study from Dose 1 to 12 months after last vaccine dose.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 01 mRNA-1273 administered through 0.2 mg/ml intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100 |
Biological: mRNA-1273
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).
Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection
|
| Experimental: Arm 02 0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100 |
Biological: mRNA-1273.351
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike (S) protein of the B.1.351 variant SARS-CoV-2 strain.
Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection
|
| Experimental: Arm 03 0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100 |
Biological: mRNA-1273.351
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike (S) protein of the B.1.351 variant SARS-CoV-2 strain.
Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection
|
| Experimental: Arm 04 0.2 mg/ml of mRNA-1273.617.2 and 0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100 |
Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Biological: mRNA-1273.617.2
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.617.2 (Delta) variant SARS-CoV-2 strain.
Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection
|
| Experimental: Arm 05 0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100 |
Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection
|
| Experimental: Arm 06 0.2 mg/ml of mRNA-1273.529 and mRNA-1273 0.2 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=100 |
Biological: mRNA-1273
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).
Biological: mRNA-1273.529
Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Other: Sodium Chloride, 0.9%
0.9% Sodium Chloride Injection
|
| Experimental: Arm 07 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Biological: BNT162b2
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.
|
| Experimental: Arm 08 500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Biological: BNT162b2 (B.1.1.529)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
Biological: BNT162b2 (B.1.351)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.
|
| Experimental: Arm 09 500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Biological: BNT162b2 (B.1.1.529)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
|
| Experimental: Arm 10 500 mcg/mL of BNT162b2 (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Biological: BNT162b2 (B.1.351)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.
|
| Experimental: Arm 11 500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Biological: BNT162b2
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.
Biological: BNT162b2 (B.1.351)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.
|
| Experimental: Arm 12 500 mcg/mL of BNT162b2 (Omicron) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Biological: BNT162b2
A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.
Biological: BNT162b2 (B.1.1.529)
A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.
|
| Experimental: Arm 13 500 mcg/mL CoV2 preS dTM-AS03 [D614] (prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Drug: AS03
AS03 oil-in-water emulsion adjuvant.
Biological: CoV2 preS dTM/D614
Is a liquid formulation made of recombinant protein placed in a formulation buffer. The antigen solution contains the spike protein sequence of the ancestral strain of SARS-CoV-2.
|
| Experimental: Arm 14 500 mcg/mL CoV2 preS dTM-AS03 [B.1.351] (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Drug: AS03
AS03 oil-in-water emulsion adjuvant.
Biological: CoV2 preS dTM [B.1.351]
Is a liquid formulation made of recombinant protein placed in a formulation buffer that contains the spike protein sequence of the B.1.351 (Beta) variant SARS-CoV-2 strain.
|
| Experimental: Arm 15 500 mcg/mL CoV2 preS dTM-AS03 [D614 + B.1.351] (prototype + Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; > / = 65 years (~45% in > / = 65 years) N=50 |
Drug: AS03
AS03 oil-in-water emulsion adjuvant.
Biological: CoV2 preS dTM/D614+B.1.351
Is a liquid formulation made of recombinant protein placed in a formulation buffer contains the spike protein sequences of the ancestral and B.1.351 (Beta) variant SARS-CoV-2 strains
|
Outcome Measures
Primary Outcome Measures
- Change from baseline in Geometric Mean Fold Rise (GMFR) [Day 1 through Day 366]
As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.
- Change from baseline in Geometric Mean Titers (GMT) [Day 1 through Day 366]
As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.
- Change in Geometric Mean Ratio [Day 1 through Day 366]
As measured by Immunoglobin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA) or Multiplex Meso Scale Discovery (MSD) antibody binding assays to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Neutralization titers will be calculated by neutralization assays using SARS-CoV-2 variant-specific S-pseudotyped viruses and different strains of live SARS-CoV-2.
Secondary Outcome Measures
- Adverse Events (AEs) leading to withdrawal from the study [Day 1 through Day 366]
- Incidence of Adverse Events of Special Interest (AESI) [Day 1 through Day 366]
- Incidence of Medically Attended Adverse Events (MAAEs) [Day 1 through Day 366]
- Incidence of New Onset Chronic Medical Conditions (NOCMCs) [Day 1 through Day 366]
- Incidence of Serious Adverse Events (SAE) [Day 1 through Day 366]
- Incidence of Solicited Adverse Events [Day 1 through Day 8]
Local and systemic events
- Incidence of Unsolicited Adverse Events [Day 1 through Day 29]
Eligibility Criteria
Criteria
Inclusion Criteria:
Participants must meet all of the following criteria to be eligible to participate in this study:
-
Individuals > / = 18 years of age at the time of consent.
-
Confirmed receipt of a complete primary and booster COVID-19 vaccine series, either homologous or heterologous, with a Federal Drug Administration (FDA) authorized/approved vaccine at least 16 weeks prior to study vaccine dose 1.
-
Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.
-
Determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health.
Note: Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment, can be included at the discretion of the investigator.
Exclusion Criteria:
Participants meeting any of the following criteria will be excluded from the study:
-
Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection < 16 weeks prior to any study vaccine dose.
-
Pregnant or breastfeeding participants.
-
Prior administration of an investigational coronavirus vaccine at any time or SARS-CoV-2 immunoglobulin, monoclonal antibody or plasma antibody therapy in the preceding 3 months.
Note: subjects that participated in clinical trials of products that are now FDA approved/authorized are allowed to participate.
-
Current/planned simultaneous participation in another interventional study or receipt of any investigational study product within 28 days prior to vaccine study dose(s).
-
A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine, polyethylene glycol (PEG), polysorbate, or nanolipid particles.
-
A history of myocarditis or pericarditis at any time prior to enrollment (for subjects in stages 1 and 2).
-
Received or plans to receive a vaccine within 28 days prior to or after any dose of study vaccine.
Note: Receipt of seasonal influenza vaccine is allowed at any time.
-
Bleeding disorder diagnosed by a healthcare provider (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or bleeding difficulties with intramuscular injections or blood draws.
-
Current or previous diagnosis of an immunocompromising condition or other immunosuppressive condition.
-
Advanced liver or kidney diseases.
-
Advanced (CD4 count < 200) and/or untreated HIV, untreated Hepatitis B or untreated Hepatitis C.
-
Received oral, intramuscular or intravenous systemic immunosuppressants, or immune-modifying drugs for >14 days in total within 6 months prior to any study vaccine dose (for corticosteroids > / = 20 mg/day of prednisone equivalent).
-
Received immunoglobulin or blood-derived products, within 3 months prior any study vaccine dose.
-
Received chemotherapy, immunotherapy or radiation therapy within 6 months prior to any study vaccine dose.
-
Study personnel or an immediate family member or household member of study personnel.
-
Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as > / = 38.0 degrees Celsius /100.4 degrees Fahrenheit). Participants meeting this criterion may be rescheduled within the relevant window periods.
Note: Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator, as long as the illness is not suggestive of COVID-19.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham School of Medicine - Alabama Vaccine Research Clinic | Birmingham | Alabama | United States | 35294 |
| 2 | University of California, San Diego - Antiviral Research Center | San Diego | California | United States | 92103-8208 |
| 3 | Zuckerberg San Francisco General Hospital, UCSF Positive Health Program | San Francisco | California | United States | 94110-2859 |
| 4 | The George Washington University Medical Faculty Associates - Infectious Diseases | Washington | District of Columbia | United States | 20037-3201 |
| 5 | Howard University - Department of Medicine - Division of Infectious Disease | Washington | District of Columbia | United States | 20060 |
| 6 | Morehouse School of Medicine - Clinical Research Center | Atlanta | Georgia | United States | 30310 |
| 7 | Emory Children's Center - Pediatric Infectious Diseases | Atlanta | Georgia | United States | 30322-1014 |
| 8 | Emory Vaccine Center - The Hope Clinic | Decatur | Georgia | United States | 30030-1705 |
| 9 | University of Illinois at Chicago College of Medicine - Division of Infectious Diseases | Chicago | Illinois | United States | 60612 |
| 10 | University of Iowa Hospitals & Clinics - Department of Internal Medicine | Iowa City | Iowa | United States | 52242 |
| 11 | Tulane University Clinical Translational Unit | New Orleans | Louisiana | United States | 70112 |
| 12 | Brigham and Women's Hospital - Infectious Diseases | Boston | Massachusetts | United States | 02115-6110 |
| 13 | Saint Louis University - Center for Vaccine Development | Saint Louis | Missouri | United States | 63104-1015 |
| 14 | Washington University School of Medicine in St. Louis - Infectious Disease Clinical Research Unit | Saint Louis | Missouri | United States | 63110 |
| 15 | NYU Grossman School, NYU Langone Vaccine Center, Long Island | Mineola | New York | United States | 11501 |
| 16 | NYU Langone Vaccine Center Research Clinic, Manhattan | New York | New York | United States | 10016 |
| 17 | University of Rochester Medical Center - Vaccine Research Unit | Rochester | New York | United States | 14642-0001 |
| 18 | Duke Human Vaccine Institute - Duke Vaccine and Trials Unit | Durham | North Carolina | United States | 27703 |
| 19 | Baylor College of Medicine - Molecular Virology and Microbiology | Houston | Texas | United States | 77030-3411 |
| 20 | University of Texas Medical Branch - Division of Infectious Disease | League City | Texas | United States | 77573 |
| 21 | Kaiser Permanente Washington Health Research Institute - Vaccines and Infectious Diseases | Seattle | Washington | United States | 98101 |
| 22 | The University of Washington - Virology Research Clinic | Seattle | Washington | United States | 98104 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 22-0004
- 5UM1AI148684-03